Integrin-linked kinase as a novel molecular switch of the IL-6-NF-κB signaling loop in breast cancer

En Chi Hsu, Samuel K. Kulp, Han Li Huang, Huang Ju Tu, Min Wu Chao, Yu Chou Tseng, Ming Chen Yang, Santosh B. Salunke, Nicholas J. Sullivan, Wen Chung Chen, Jianying Zhang, Che Ming Teng, Wen Mei Fu, Duxin Sun, Max S. Wicha, Charles L. Shapiro, Ching Shih Chen

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Abstract

Substantial evidence has clearly demonstrated the role of the IL-6-NF-κB signaling loop in promoting aggressive phenotypes in breast cancer. However, the exact mechanism by which this inflammatory loop is regulated remains to be defined. Here, we report that integrin-linked kinase (ILK) acts as a molecular switch for this feedback loop. Specifically, we show that IL-6 induces ILK expression via E2F1 upregulation, which, in turn, activates NF-κB signaling to facilitate IL-6 production. shRNAmediated knockdown or pharmacological inhibition of ILK disrupted this IL-6-NF-κB signaling loop, and blocked IL-6-induced cancer stem cells in vitro and estrogen-independent tumor growth in vivo. Together, these findings establish ILK as an intermediary effector of the IL-6-NF-κB feedback loop and a promising therapeutic target for breast cancer.

Original languageEnglish
Pages (from-to)430-442
Number of pages13
JournalCarcinogenesis
Volume37
Issue number4
DOIs
Publication statusPublished - Oct 29 2015
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research

Cite this

Hsu, E. C., Kulp, S. K., Huang, H. L., Tu, H. J., Chao, M. W., Tseng, Y. C., Yang, M. C., Salunke, S. B., Sullivan, N. J., Chen, W. C., Zhang, J., Teng, C. M., Fu, W. M., Sun, D., Wicha, M. S., Shapiro, C. L., & Chen, C. S. (2015). Integrin-linked kinase as a novel molecular switch of the IL-6-NF-κB signaling loop in breast cancer. Carcinogenesis, 37(4), 430-442. https://doi.org/10.1093/carcin/bgw020